The major adducts of cis and trans benzo[a]pyrene diol epoxides cause chain termination during DNA synthesis in vitro.

We have studied DNA synthesis in vitro using as template phi X174 DNA containing varying numbers of adducts formed by reaction with cis and trans benzo[a]pyrene (BP) diol-epoxides. The extent of DNA synthesis decreases with increasing numbers of adducts and there is a concomitant decrease in the size of the DNA products. Both decreases can be accounted for quantitatively by the assumption that synthesis terminates at every BP adduct. Since the majority of the adducts are located at the 2-amino group of guanine, we deduce that these adducts cause termination. The role of adducts at other sites is uncertain. The cis and trans BP diol-epoxides are indistinguishable with regard to chain termination, yet in vivo these isomers behave differently. These results suggest that chain determination alone is insufficient to account for the mutagenic effects of BP diol-epoxides.